Fungi have long been recognized as instigators of plant diseases associated with the elaboration of one or more phytotoxins. To date, phytotoxins having the unique property of expressing host specificity at the species or cultivar level are known only from pathogens of crop plants. This is probably due to the fact that agrosystems with a strictly homogeneous genetic base serve as a huge reservoir of essentially identical plant material. This homogeneity renders such species susceptible to widespread devastation by one or more pathogens.
The 1970 Southern corn leaf blight epidemic in the U.S.-Canada, attributed to the pathogenic fungus Dreschlera maydis, is a case in point (Tatum, L. A. (1971) Science 171, 1113-1115). Thus, a pathogen has the potential to develop and spread quickly under such conditions and can easily be observed and isolated. Common weedy plants, however, usually exist in a population having a broad, mixed genetic base which tends to preclude the development of such an epidemic, making discovery of the pathogen difficult, if not impossible.
The detection and study of weed pathogens is important not only for their intrinsic ability to serve as biocontrol agents, but also because of their propensity to produce novel bioactive substances. These substances could become novel herbicides or provide important chemical leads to the herbicide industry (Strobel, G. A., Sugawara, F. & Clardy, J. (1987), in Allelochemica: Role in Agriculture and Forestry, ed. Waller, G. R. (American Chemical Society, Washington, 516-523).
Spotted knapweed (Centaurea maculosa) now poses a significant threat as a weed species, having invaded rangelands of the northwestern United States and southwestern Canada. Since its introduction to the United States in the early 1900's, this hardy composite has occupied millions of acres with an estimated 70% decline in forage production (Harris, P. & Cranston, R. (1979) Can. J. Plant Sci. 59, 375-382). Its rapid spread has been aided by a lack of natural predators in North America and by an ability to compete successfully with native grasses (Myers, J. H. & Berube, D. E. (1983) Can. J. Plant Sci. 63, 981-987).
Diketopiperazines are in general known in the art (See for example Patent Publication No. DD-224216 (Dec. 30, 1981)). However, the diketopiperazines described in this reference are a general group of diketopiperazines utilized as substrates for the preparation of N-lysergic aminoacylactam derivatives. No phytotoxic activity is described in the reference for these compounds. The isolation and identification of a host specific toxin against an important weed pest has important biological implications.
Various form species of A. alternata have been credited with production of host specific phytotoxins for crop plants. To date, several such toxins have been isolated and identified from various pathotypes of this organism (Nishimura, S. & Kohmoto, K. (1983) Ann. Rev. Phytopathol. 21, 87-116).
Several host specific toxins isolated to date from Alternaria alternata include compounds that are active against important cultivars of a variety of crop plants such as pears, apples, citrus, and tomatoes (Itoh, M., Hagiwara, D. & Kamiya, T. (1975) Tetrahedron Letters 49, 4393-4394). The value of a highly specific toxin to economically desirable plants resides not only in its herbicidal potential but in its utility as a screening agent. Cultivars of a particular plant can be challenged by the toxin and resistant individuals can be disseminated (Strobel, G. A. (1982) Ann. Rev. Biochem. 51, 309-333).
However, the discovery of a weed specific toxin represents an even more compelling possibility as a direct biocontrol agent.